Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors

Yeon Sun Lee, Robert Kupp, Michael V. Remesic, Cyf Ramos-Colon, Sara M Hall, Christopher Chan, David Rankin, Josephine Lai, Frank Porreca, Victor J. Hruby

Research output: Contribution to journalLetter

2 Scopus citations

Abstract

As a unique endogenous opioid ligand, dynorphin A shows paradoxical neuroexcitatory effects at bradykinin receptors, and the effects are known to be amplified by the upregulation of dynorphin A under chronic pain and inflammatory conditions. In our earlier structure–activity relationship studies, the amphipathic dynorphin A fragment, [Des-Arg7]-Dyn A-(4–11), was identified as a pharmacophore for the bradykinin receptors along with key structural features. Here, further modifications of the pharmacophore showed that the position of a Pro residue is also an important feature because of its role in making (or disrupting) a β-turn or 310 helix structure which is crucial for receptor recognition.

Original languageEnglish (US)
Pages (from-to)615-619
Number of pages5
JournalChemical Biology and Drug Design
DOIs
StatePublished - Oct 1 2016

Keywords

  • amphipathicity
  • bradykinin receptors
  • chronic pain
  • non-opioid dynorphin A
  • proline
  • structure–activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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